Table of Contents
- Overview of Clinical Trials
- Chondrosarcoma Research
- Pediatric Cancer Studies
- Advanced Solid Tumors Investigation
- Hodgkin Lymphoma Trial
- Primary Outcomes and Measurements
- Safety Monitoring and Adverse Events
- Patient Participation and Eligibility
Overview of Clinical Trials
Clinical trials investigating 1,3-BUTYLENE GLYCOL are part of comprehensive cancer treatment research programs. This substance appears as a component in combination therapy regimens being studied across multiple cancer types[1][2][3][4]. The trials span different phases of clinical research, from early safety studies to larger effectiveness evaluations.
These studies represent important advances in cancer treatment research, particularly for cancers that are difficult to treat with conventional therapies. The trials include both adult and pediatric populations, addressing a range of malignancies from rare bone cancers to more common blood cancers[1][2][3][4].
Chondrosarcoma Research
Study Design and Population
A Phase 2 clinical trial (NCT04950075) is investigating treatment for conventional chondrosarcoma, a type of cancer affecting bones and joints[1]. This study focuses on patients whose cancer cannot be surgically removed (unresectable) or has spread to other parts of the body (metastatic)[1]. The trial has authorized enrollment of 201 adult participants, making it one of the larger studies in this research program[1].
Treatment Combination
The trial uses a combination of medications including[1]:
- ACETYLCYSTEINE administered orally at 1200 mg
- DEXAMETHASONE given orally at 8 mg
- DIPHENHYDRAMINE administered intravenously at 50 mg
- GLUCOSE given as intravenous infusion at 250 ml
- OZEKIBART administered intravenously at 3 mg/kg body weight
Primary Research Goal
The main objective of this study is to evaluate anticancer effectiveness by measuring Progression Free Survival (PFS)[1]. Researchers use standardized measurement criteria called RECIST v1.1 (Response Evaluation Criteria in Solid Tumors Version 1.1) to assess how long patients live without their cancer getting worse[1]. The evaluation is conducted by central real-time independent radiology review to ensure objective assessment[1].
The study compares the treatment combination containing OZEKIBART against placebo in the Intention To Treat (ITT) population, which includes all enrolled patients regardless of whether they complete the full treatment course[1].
Pediatric Cancer Studies
Study Overview
A Phase 1 clinical trial (2024-518771-66-00) is investigating patritumab deruxtecan (HER3-DXd) in children with cancer[2]. This study focuses on two specific childhood cancers: hepatoblastoma (liver cancer) and rhabdomyosarcoma (muscle cancer)[2]. The trial has authorized enrollment of 79 pediatric participants[2].
Study Structure
The trial is divided into two parts with distinct objectives[2]:
- Part 1 focuses on evaluating safety and tolerability while establishing a preliminary recommended Phase 2 dose (RP2D)
- Part 1 also characterizes the pharmacokinetics (how the drug moves through the body)
- Parts 1 and 2 evaluate preliminary antitumor effects measured by objective response rate according to RECIST 1.1
Treatment Components
The study includes[2]:
- MK-1022 administered intravenously
- DEXAMETHASONE used as supportive medication
- Additional supportive medications administered by various routes
Comprehensive Safety Assessment
Part 1 of the study measures multiple safety and pharmacokinetic parameters[2]:
- Percentage of participants experiencing dose-limiting toxicities (DLTs)
- Percentage of participants experiencing any adverse event
- Percentage of participants who discontinue treatment due to adverse events
- Area Under the Curve (AUC) measurements for total anti-HER3 antibody, antibody-conjugated drug, and free drug in plasma
- Maximum Concentration (Cmax) measurements for all drug components
- Trough concentration (Ctrough) measurements taken immediately before the next dose
These detailed measurements help researchers understand how the drug behaves in children’s bodies and identify the safest and most effective dose[2].
Advanced Solid Tumors Investigation
Trial Design
A Phase 1/2 study (NCT03715933) is investigating treatment for patients with advanced or metastatic solid tumors, with particular focus on sarcomas[3]. This trial has authorized enrollment of 132 participants including both adults and adolescents[3].
Target Populations
The study specifically addresses[3]:
- Ewing sarcoma (a rare bone and soft tissue cancer)
- Colorectal adenocarcinoma (colon and rectal cancer)
- Succinate dehydrogenase (SDH)-deficient solid tumors
- Gastrointestinal stromal tumor (GIST)
Treatment Regimens
The trial uses OZEKIBART administered intravenously in combination with different chemotherapy regimens tailored to specific cancer types[3]:
- For Ewing sarcoma: combination with irinotecan and temozolomide (TMZ)
- For colorectal adenocarcinoma: combination with fluorouracil (FU), leucovorin, and irinotecan (FOLFIRI)
- DEXAMETHASONE administered both orally and intravenously as supportive medication
The study includes various formulations of temozolomide in different strengths (5 mg, 20 mg, 100 mg, 140 mg, 180 mg, and 250 mg hard capsules) administered orally[3]. Irinotecan is given as an intravenous infusion using a concentrated solution[3].
Primary Objectives
The study has multiple primary objectives[3]:
- Assess safety and tolerability of OZEKIBART combined with distinct chemotherapies in the target populations
- Evaluate antitumor efficacy in Ewing sarcoma by measuring overall response rate (ORR) and duration of response (DOR)
- Evaluate antitumor efficacy in colorectal adenocarcinoma using the same measurements
- Monitor treatment-emergent adverse events (TEAEs) including determination of dose-limiting toxicities and serious adverse events
- Assess clinical response per RECIST v1.1 criteria
Adverse event severity is assigned using the NCI CTCAE v5.0 (National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0), a standardized grading system[3].
Hodgkin Lymphoma Trial
Study Concept
A Phase 2 trial (NCT03517137) conducted by EORTC (European Organisation for Research and Treatment of Cancer) is investigating very early FDG-PET-response adapted targeted therapy for advanced Hodgkin lymphoma[4]. This single-arm study has authorized enrollment of 7 participants[4].
Treatment Approach
The study uses a treatment adaptation strategy based on very early imaging results from FDG-PET/CT scans[4]. The goal is to improve treatment effectiveness while minimizing toxicity by tailoring therapy based on how quickly patients respond[4].
Treatment includes brentuximab vedotin (BV)-containing regimens called BrAVD and BrECADD[4]. The medication components include[4]:
- ADCETRIS (brentuximab vedotin) 50 mg powder for concentrate, administered as infusion at 550 mg
- DACARBAZINE given as infusion at 525 mg
- DOXORUBICIN administered as infusion at 550 mg
- DEXAMETHASONE given orally at 40 mg
- VINBLASTINE administered as infusion at 7.4 mg
- CYCLOPHOSPHAMIDE given as infusion at 262.5 mg
- ETOPOSIDE administered as infusion at 315 mg
Primary Endpoint
The study measures modified progression-free survival rate at 2 years after treatment start (2yr-mPFS)[4]. Events counted for this endpoint include[4]:
- Disease progression or relapse
- Starting new treatment for classical Hodgkin lymphoma when not in complete remission after completing protocol treatment
- Death from any cause
Primary Outcomes and Measurements
Progression-Free Survival
Progression-free survival (PFS) is a critical outcome measure in cancer clinical trials[1]. It represents the time from treatment start until cancer progression or death, whichever occurs first[1]. The chondrosarcoma trial uses this as its primary endpoint, with assessment performed by independent radiologists to ensure objectivity[1].
Objective Response Rate
Objective response rate (ORR) measures the proportion of patients whose tumors shrink or disappear in response to treatment[2][3]. This includes both complete responses (tumor completely disappears) and partial responses (tumor shrinks by a specified amount)[2][3]. The pediatric trial and solid tumors study both use ORR as a primary outcome measure[2][3].
Duration of Response
Duration of response (DOR) measures how long the beneficial effects of treatment last[3]. In the advanced solid tumors trial, DOR is assessed alongside ORR to provide a complete picture of treatment effectiveness in Ewing sarcoma and colorectal adenocarcinoma[3].
Modified Progression-Free Survival
The Hodgkin lymphoma trial uses a modified progression-free survival rate at 2 years[4]. This adaptation accounts for additional events beyond traditional progression and death, including the need to start alternative treatments when patients don’t achieve complete remission[4].
RECIST v1.1 Criteria
Multiple trials use RECIST v1.1 (Response Evaluation Criteria in Solid Tumors version 1.1) as the standardized method for measuring tumor response[1][2][3]. This system provides consistent criteria for determining whether tumors are growing, shrinking, or remaining stable during treatment[1][2][3].
Safety Monitoring and Adverse Events
Dose-Limiting Toxicities
Dose-limiting toxicities (DLTs) are serious side effects that prevent further dose increases[2][3]. The pediatric trial specifically measures the percentage of participants experiencing DLTs as a primary outcome in Part 1[2]. Identifying DLTs is crucial for determining the maximum safe dose, particularly important in children where dosing must be carefully calibrated[2].
Adverse Event Monitoring
All trials include comprehensive adverse event monitoring[2][3]. The pediatric study tracks[2]:
- Percentage of participants experiencing any adverse event
- Percentage who discontinue treatment due to adverse events
The advanced solid tumors trial monitors treatment-emergent adverse events (TEAEs) including both DLTs and serious adverse events (SAEs)[3]. Severity grading follows the NCI CTCAE v5.0 standardized system, which classifies adverse events on a scale from mild to life-threatening[3].
Pharmacokinetic Assessments
The pediatric trial includes detailed pharmacokinetic (PK) measurements to understand how the drug behaves in children’s bodies[2]. These assessments measure[2]:
- Area Under the Curve (AUC) for total antibody, conjugated drug, and free drug components
- Maximum Concentration (Cmax) showing peak drug levels in blood
- Trough concentration (Ctrough) measuring drug levels just before the next dose
These measurements are performed using liquid chromatography-mass spectrometry (LC-MS), a highly precise analytical technique[2]. Understanding these parameters helps researchers optimize dosing schedules and predict drug behavior in different patient populations[2].
Patient Participation and Eligibility
Adult Populations
The chondrosarcoma trial enrolls adults with unresectable or metastatic conventional chondrosarcoma[1]. With 201 authorized participants, this represents a substantial patient population for a rare cancer type[1].
The advanced solid tumors study includes both adults and adolescents, with 132 authorized participants[3]. This trial targets multiple cancer types including Ewing sarcoma, colorectal adenocarcinoma, SDH-deficient solid tumors, and GIST[3].
Pediatric Populations
The pediatric cancer study specifically enrolls children with hepatoblastoma or rhabdomyosarcoma[2]. With 79 authorized participants, this trial represents significant research in childhood cancers[2].
Specialized Populations
The Hodgkin lymphoma trial focuses on patients with advanced stage disease[4]. With 7 authorized participants, this smaller study allows for intensive monitoring of the response-adapted treatment approach[4].
Study Status
All four trials have “Authorised” status, meaning they have received regulatory approval to proceed[1][2][3][4]. However, authorization does not necessarily mean active recruitment is ongoing. Patients interested in participation should contact trial sites or their healthcare providers for current enrollment status and specific eligibility requirements.
Interventional Study Design
All trials are classified as interventional studies, meaning participants receive specific treatments as part of the research protocol[1][2][3][4]. This differs from observational studies where researchers simply monitor outcomes without providing specific interventions[1][2][3][4].
